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Identification of an Aging-Related Gene Signature in Predicting Prognosis and Indicating Tumor Immune Microenvironment in Breast Cancer

Breast cancer (BC) is the most commonly diagnosed malignancy accompanied by high invasion and metastasis features. Importantly, emerging studies have supported that aging is a key clue that participates in the immune state and development of BC. Nevertheless, there are no studies concerning the agin...

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Autores principales: Lv, Wenchang, Zhao, Chongru, Tan, Yufang, Hu, Weijie, Yu, Honghao, Zeng, Ning, Zhang, Qi, Wu, Yiping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716799/
https://www.ncbi.nlm.nih.gov/pubmed/34976839
http://dx.doi.org/10.3389/fonc.2021.796555
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author Lv, Wenchang
Zhao, Chongru
Tan, Yufang
Hu, Weijie
Yu, Honghao
Zeng, Ning
Zhang, Qi
Wu, Yiping
author_facet Lv, Wenchang
Zhao, Chongru
Tan, Yufang
Hu, Weijie
Yu, Honghao
Zeng, Ning
Zhang, Qi
Wu, Yiping
author_sort Lv, Wenchang
collection PubMed
description Breast cancer (BC) is the most commonly diagnosed malignancy accompanied by high invasion and metastasis features. Importantly, emerging studies have supported that aging is a key clue that participates in the immune state and development of BC. Nevertheless, there are no studies concerning the aging-related genes (AGs) in constructing the prognosis signature of BC. Here, to address this issue, we initially performed a systematic investigation of the associations between AGs and BC prognosis and accordingly constructed a prognosis risk model with 10 AGs including PLAU, JUND, IL2RG, PCMT1, PTK2, HSPA8, NFKBIA, GCLC, PIK3CA, and DGAT1 by using the least absolute shrinkage and selection operator (LASSO) regression and Cox regression analysis. Meanwhile, our analysis further confirmed that the nomogram possessed a robust performance signature for predicting prognosis compared to clinical characteristics of BC patients, including age, clinical stage, and TNM staging. Moreover, the risk score was confirmed as an independent prognostic index of BC patients and was potentially correlated with immune scores, estimate score, immune cell infiltration level, tumor microenvironment, immunotherapy effect, and drug sensitivity. Furthermore, in the external clinical sample validation, AGs were expressed differentially in patients from different risk groups, and tumor-associated macrophage markers were elevated in high-risk BC tissues with more co-localization of AGs. In addition, the proliferation, transwell, and wound healing assays also confirmed the promoting effect of DGAT1 in BC cell proliferation and migration. Therefore, this well-established risk model could be used for predicting prognosis and immunotherapy in BC, thus providing a powerful instrument for combating BC.
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spelling pubmed-87167992021-12-31 Identification of an Aging-Related Gene Signature in Predicting Prognosis and Indicating Tumor Immune Microenvironment in Breast Cancer Lv, Wenchang Zhao, Chongru Tan, Yufang Hu, Weijie Yu, Honghao Zeng, Ning Zhang, Qi Wu, Yiping Front Oncol Oncology Breast cancer (BC) is the most commonly diagnosed malignancy accompanied by high invasion and metastasis features. Importantly, emerging studies have supported that aging is a key clue that participates in the immune state and development of BC. Nevertheless, there are no studies concerning the aging-related genes (AGs) in constructing the prognosis signature of BC. Here, to address this issue, we initially performed a systematic investigation of the associations between AGs and BC prognosis and accordingly constructed a prognosis risk model with 10 AGs including PLAU, JUND, IL2RG, PCMT1, PTK2, HSPA8, NFKBIA, GCLC, PIK3CA, and DGAT1 by using the least absolute shrinkage and selection operator (LASSO) regression and Cox regression analysis. Meanwhile, our analysis further confirmed that the nomogram possessed a robust performance signature for predicting prognosis compared to clinical characteristics of BC patients, including age, clinical stage, and TNM staging. Moreover, the risk score was confirmed as an independent prognostic index of BC patients and was potentially correlated with immune scores, estimate score, immune cell infiltration level, tumor microenvironment, immunotherapy effect, and drug sensitivity. Furthermore, in the external clinical sample validation, AGs were expressed differentially in patients from different risk groups, and tumor-associated macrophage markers were elevated in high-risk BC tissues with more co-localization of AGs. In addition, the proliferation, transwell, and wound healing assays also confirmed the promoting effect of DGAT1 in BC cell proliferation and migration. Therefore, this well-established risk model could be used for predicting prognosis and immunotherapy in BC, thus providing a powerful instrument for combating BC. Frontiers Media S.A. 2021-12-16 /pmc/articles/PMC8716799/ /pubmed/34976839 http://dx.doi.org/10.3389/fonc.2021.796555 Text en Copyright © 2021 Lv, Zhao, Tan, Hu, Yu, Zeng, Zhang and Wu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Lv, Wenchang
Zhao, Chongru
Tan, Yufang
Hu, Weijie
Yu, Honghao
Zeng, Ning
Zhang, Qi
Wu, Yiping
Identification of an Aging-Related Gene Signature in Predicting Prognosis and Indicating Tumor Immune Microenvironment in Breast Cancer
title Identification of an Aging-Related Gene Signature in Predicting Prognosis and Indicating Tumor Immune Microenvironment in Breast Cancer
title_full Identification of an Aging-Related Gene Signature in Predicting Prognosis and Indicating Tumor Immune Microenvironment in Breast Cancer
title_fullStr Identification of an Aging-Related Gene Signature in Predicting Prognosis and Indicating Tumor Immune Microenvironment in Breast Cancer
title_full_unstemmed Identification of an Aging-Related Gene Signature in Predicting Prognosis and Indicating Tumor Immune Microenvironment in Breast Cancer
title_short Identification of an Aging-Related Gene Signature in Predicting Prognosis and Indicating Tumor Immune Microenvironment in Breast Cancer
title_sort identification of an aging-related gene signature in predicting prognosis and indicating tumor immune microenvironment in breast cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8716799/
https://www.ncbi.nlm.nih.gov/pubmed/34976839
http://dx.doi.org/10.3389/fonc.2021.796555
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